Science· 2026Q1
Early-life colonization with Clostridioides difficile remodels the developing gut
- 2citations
- Q1SCImago
- 2026year
Short summary
Early-life colonization with *Clostridioides difficile* in mice permanently reshapes the developing gut epithelium, enriching injury-associated stem cells and skewing differentiation towards secretory lineages, even after transient colonization.
AI-generated from the title and abstract; the full text is not read.
Key points
- Neonatal *C. difficile* colonization in mice induced persistent changes in intestinal epithelium into adulthood.
- Colonization enriched injury-associated intestinal stem cell populations and skewed differentiation toward secretory lineages.
- Epithelial responses were dependent on *C. difficile* toxins.
- Maternal vaccination with a *C. difficile*-targeted mRNA-lipid nanoparticle vaccine protected neonates.
- Human infant intestinal epithelial cells showed sensitivity to *C. difficile* toxins.
AI-generated from the title and abstract; the full text is not read.
Abstract
Clostridioides difficile causes severe disease in adults but commonly colonizes infants asymptomatically. The consequences of early-life colonization on host development remain unknown. In a neonatal mouse model, C. difficile colonization drove proinflammatory and tissue repair responses in the intestinal epithelium, enriching injury-associated intestinal stem cell populations and skewing differentiation toward secretory lineages. Despite transient colonization, exposure to C. difficile early in life led to persistent changes into adulthood. Epithelial responses were toxin dependent, as colonization with nontoxigenic strains or maternal vaccination with a C. difficile –targeted messenger RNA–lipid nanoparticle vaccine protected neonates. Human infant intestinal epithelial cells were sensitive to C. difficile toxins, and biopsies from colonized infants exhibited altered intestinal stem cell behavior. This study redefines C. difficile as an underappreciated early-life pathogen with lasting effects on host development.
The authors' abstract, as published at the source. Science, 2026 · DOI ↗
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Field: Infectious Diseases
Infectious DiseasesMedicine